Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form

Abstract

The aim of this research was to use a ram extruder to prepare directly a fast release dosage form with uniform shape and density, containing carbamazepine (C) as a water-insoluble drug and polyethylene glycol 4000 (PEG) as a low melting binder. The potential inclusion of lactose (L) as a hydrophilic filler was also considered. The temperature suitable to ensure a successful extrusion process of several formulations containing PEG in different percentages was found to be below the melting point of the PEG. The influence of composition on the extrusion process of different ram speeds was checked by measuring the pressure at the steady state, the apparent shear rate and the apparent shear stress of a range of mixtures of drug, lactose and PEG. The physical–mechanical properties of extrudates, including tensile strength and Young's modulus, prepared with different ram velocities were also determined. The solid-state physical structure by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) was established. The dissolution of the extrudates and their corresponding physical mixtures were compared. The mixtures were found to be shear thinning when extruded; the tensile strength of extrudates was dependent on the composition but not the extrusion rate, while the value of Young's modulus was strongly influenced by the rate of extrusion, but less affected by the composition of the extrudates. The results of DSC and XRD indicated that the solid structure of the extrudates corresponded to that of a physical mixture of the components, hence there had been no change in the physical form of the drug induced by extrusion. In terms of dissolution, the rate of the extrusion process did not influence the performance of the products, whereas the composition did. The extruded mixtures of an equivalent composition exhibited a more rapid release than a simple physical mixture. The addition of lactose reduced the dissolution rate.